title: Influence of endotoxin on contractility in the rat gastric fundus.
abstract: The influence of in vivo treatment with E. coli lipopolysaccharide endotoxin on the contractility of the rat gastric fundus was studied. Four h after lipopolysaccharide treatment (20 mg/kg i.p.), the contractile responses to prostaglandin F2alpha in longitudinal muscle strips from the gastric fundus were not different from those in control animals, while the well-known decreased response to noradrenaline in rings of the thoracic aorta was confirmed. Incubation of the tissues with L-arginine did not depress the response to prostaglandin F2alpha in fundus strips of lipopolysaccharide-treated rats. Twelve h after lipopolysaccharide treatment (6.7 mg/kg i.p.), the prostaglandin F2alpha-induced contractions were consistently depressed. The impairment of the prostaglandin F2alpha-induced responses by lipopolysaccharide treatment was not reversed by the nitric oxide synthase inhibitors NG-nitro-L-arginine (L-NNA, 10(-4) M), NG-nitro-L-arginine methyl ester (L-NAME, 3 x 10(-4) M), aminoguanidine (10(-4) M) and L-N6-l-iminoethyl-lysine (L-NIL, 10(-4) M) nor by the cyclooxygenase inhibitor indomethacin (10(-5) M). The impairment was prevented by pretreating the animals with dexamethasone (5 mg/kg i.p.), which had no effect per se on the contractile response to prostaglandin F2alpha. Lipopolysaccharide treatment did not influence the contractile responses to KCl and serotonin. The nonadrenergic noncholinergic relaxant responses to transmural electrical stimulation were not influenced 4 h after lipopolysaccharide treatment but were moderately reduced after 12 h. The results illustrate that the selective impairment of prostaglandin F2alpha-induced contractions in the rat gastric fundus by lipopolysaccharide treatment is not mediated via generation of nitric oxide; downregulation of the prostaglandin F2alpha-receptor by lipopolysaccharide treatment might be involved.
authors.affiliation: Heymans Institute of Pharmacology, University of Gent, Belgium. romain.lefebvre@rug.ac.be
authors.forename: R A
authors.initials: RA
authors.lastname: Lefebvre
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology; D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D004731:Endotoxins; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D015237:Dinoprost